An Efficacy and Safety Study of Vedolizumab Intravenous (IV) Compared to Adalimumab Subcutaneous (SC) in Participants With Ulcerative Colitis

• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) treatment compared to adalimumab subcutaneous (SC) treatment over a 52-week treatment period.

Condition or disease	Intervention/treatment	Phase
Colitis, Ulcerative	Drug: Vedolizumab; Drug: Adalimumab placebo; Drug: Adalimumab; Drug: Vedolizumab placebo	Phase 3

Detailed Description:

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to treat people who have ulcerative colitis. This study will look at the stool frequency, rectal bleeding and findings on endoscopy of people who take vedolizumab compared to those who take adalimumab.

The study will enroll approximately 658 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Vedolizumab 300 mg IV
• Adalimumab 160 mg on Day 1 followed by 80 mg on Week 2 then 40 mg every 2 weeks SC

All participants will receive 1 intravenous infusion on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. All participants will also receive 4 SC injections on Day 1 or 2 SC injections each on Days 1 and 2, followed by 2 SC injections in 1 day on Week 2 and then 1 SC injection every 2 weeks for up to Week 50. All participants will be asked to record the symptoms of ulcerative colitis in a daily diary.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 79 weeks. Participants will make approximately 11 visits to the clinic, and will be contacted by telephone 6 months after last dose of study drug for a follow-up assessment.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	770 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-Blind, Double-Dummy, Multicenter, Active-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab IV Compared to Adalimumab SC in Subjects With Ulcerative Colitis
Actual Study Start Date :	July 15, 2015
Actual Primary Completion Date :	September 26, 2018
Actual Study Completion Date :	January 18, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vedolizumab IV; Vedolizumab 300 milligram (mg), infusion, intravenously over 30 minutes on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46. Adalimumab placebo-matching injection, subcutaneously on Day 1, Week 2, and every 2 weeks thereafter up to Week 50.	Drug: Vedolizumab; Vedolizumab infusion; Drug: Adalimumab placebo; Adalimumab placebo-matching injection
Active Comparator: Adalimumab SC; Adalimumab 160 mg, injection, subcutaneously on Day 1, adalimumab 80 mg, injection, subcutaneously at Week 2, then adalimumab 40 mg, injection, subcutaneously every 2 weeks thereafter up to Week 50. Vedolizumab placebo-matching infusion, intravenously on Day 1 and Weeks 2, 6, 14, 22, 30, 38, and 46.	Drug: Adalimumab; Adalimumab injection; Drug: Vedolizumab placebo; Vedolizumab placebo-matching infusion

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving Clinical Remission [ Time Frame: Week 52 ]
   Clinical remission is defined as a complete Mayo score of less than or equal to (<=) 2 points and no individual subscore greater than (>) 1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consists of 4 subscores: stool frequency, rectal bleeding, findings of endoscopy, and physician global assessment, each ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe).

Secondary Outcome Measures :

1. Percentage of Participants Achieving Mucosal Healing [ Time Frame: Week 52 ]
   Mucosal healing is defined as Mayo endoscopic subscore <=1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Findings of endoscopy is a subscale of Mayo score, which ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe).
2. Percentage of Participants Using Oral Corticosteroids at Baseline who Discontinue Corticosteroids and are in Clinical Remission [ Time Frame: Week 52 ]
   Corticosteroid-free remission: participants who discontinue corticosteroids and achieve clinical remission will be assessed in participants with baseline oral corticosteroid use. Clinical remission is defined as a complete Mayo score of <=2 points and no individual subscore >1 point. Mayo score: instrument designed to measure disease activity of ulcerative colitis. Total score range: 0 to 12; higher score=more severe disease. It consists of 4 subscores: stool frequency, rectal bleeding, findings of endoscopy, and physician global assessment, each ranges from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 85 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Has a diagnosis of ulcerative colitis established at least 3 months prior to screening by clinical and endoscopic evidence and corroborated by a histopathology report.
2. Has moderately to severely active ulcerative colitis as determined by a Mayo score of 6 to 12 with an endoscopic subscore greater than or equal to >=2 within 14 days prior to the randomization.
3. Has evidence of ulcerative colitis proximal to the rectum (>=15 centimeter [cm] of involved colon).
4. With extensive colitis (up to the hepatic flexure) or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (may be performed during the Screening Period).

5. The participant:

   1. Has had previous treatment with tumor necrosis factor- alpha (TNF-alpha) antagonists without documented clinical response to treatment (example, due to lack of response [primary nonresponders], loss of response, or intolerance [secondary nonresponders]), or
   2. Has previously used a TNF-alpha antagonists (except adalimumab), and discontinued its use due to reasons other than safety, or
   3. Is naïve to TNF-alpha antagonist therapy but is failing current treatment (example, corticosteroids, 5-aminosalicylate [5-ASA], or immunomodulators).

Exclusion Criteria:

1. Clinical evidence of abdominal abscess or toxic megacolon at Screening.
2. Has had an extensive colonic resection, subtotal or total colectomy.
3. Has had ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
4. Has a diagnosis of Crohn's colitis or indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.

5. Has received any of the following for the treatment of underlying disease within 30 days of randomization:

   1. Non-biologic therapies (example, cyclosporine, tacrolimus, thalidomide) other than those specifically listed in Section Permitted Medications For Treatment of UC.
   2. An approved non-biologic therapy in an investigational protocol.
6. Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half lives prior to the screening (whichever is longer).
7. Has previously received natalizumab, efalizumab, adalimumab, AMG-181, anti-mucosal addressin cell adhesion molecule-1 antibodies, or rituximab.
8. Has previously received vedolizumab.
9. Has history or evidence of adenomatous colonic polyps that have not been removed, or colonic mucosal dysplasia.
10. Evidence of an active infection during Screening.
11. Evidence of, or treatment for, Clostridium difficile (C. difficile) or other intestinal pathogen within 28 days prior to the 1st dose of study drug.
12. Has chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection (* HBV immune participants, ie, being hepatitis B surface antigen [HBsAg], may participate).
13. Has active or latent TB, regardless of treatment history.
14. Has used a topical (rectal) treatment with (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of the administration of the 1st dose of study drug.
15. Has a positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.

Contacts and Locations

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Sponsors and Collaborators

Takeda

Investigators

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Study Director:	Medical Director	Takeda

More Information

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Responsible Party:	Takeda
ClinicalTrials.gov Identifier:	NCT02497469 History of Changes
Other Study ID Numbers:	MLN0002-3026; U1111-1168-6713 ( Registry Identifier: WHO ); 2015-000939-33 ( EudraCT Number ); NL54690.056.15 ( Registry Identifier: CCMO )
First Posted:	July 14, 2015
Last Update Posted:	April 12, 2019
Last Verified:	April 2019

Keywords provided by Takeda:

Drug Therapy

Additional relevant MeSH terms:

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Colitis; Ulcer; Colitis, Ulcerative; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases	Pathologic Processes; Inflammatory Bowel Diseases; Adalimumab; Vedolizumab; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents